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Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control.
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SYSNO ASEP 0584639 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Ostatní články Název Stem-loop-induced ribosome queuing in the uORF2/ATF4 overlap fine-tunes stress-induced human ATF4 translational control. Tvůrce(i) Smirnova, Anna (MBU-M)
Hronová, Vladislava (MBU-M) ORCID
Mohammad, Mahabub Pasha (MBU-M) RID
Herrmannová, Anna (MBU-M) RID, ORCID
Gunišová, Stanislava (MBU-M) RID
Petráčková, Denisa (MBU-M) RID, ORCID
Halada, Petr (MBU-M) RID, ORCID
Coufal, Štěpán (MBU-M) ORCID, RID
Swirski, M. (PL)
Rendleman, J. (US)
Jendruchová, Kristýna (MBU-M)
Hatzoglou, M. (US)
Beznosková, Petra (MBU-M) RID
Vogel, C. (US)
Valášek, Leoš Shivaya (MBU-M) RID, ORCIDZdroj.dok. Cell Reports. - : Cell Press - ISSN 2211-1247
Roč. 43, č. 4 (2024), s. 113976Poč.str. 26 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova ribosome ; factor 4 (ATF4) ; stress respon ; ORF2/ATF4 overlap Obor OECD Cell biology CEP GX19-25821X GA ČR - Grantová agentura ČR EH22_008/0004575 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Výzkumná infrastruktura CIISB III - 90242 - Masarykova univerzita / Středoevropský technologický institut Způsob publikování Open access Institucionální podpora MBU-M - RVO:61388971 DOI 10.1016/j.celrep.2024.113976 Anotace Activating transcription factor 4 (ATF4) is a master transcriptional regulator of the integrated stress response, leading cells toward adaptation or death. ATF4's induction under stress was thought to be due to delayed translation reinitiation, where the reinitiation-permissive upstream open reading frame 1 (uORF1) plays a key role. Accumulating evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional regulatory routes. We identified a highly conserved stem-loop in the uORF2/ATF4 overlap, immediately preceded by a near-cognate CUG, which introduces another layer of regulation in the form of ribosome queuing. These elements explain how the inhibitory uORF2 can be translated under stress, confirming prior observations but contradicting the original regulatory model. We also identified two highly conserved, potentially modified adenines performing antagonistic roles. Finally, we demonstrated that the canonical ATF4 translation start site is substantially leaky scanned. Thus, ATF4's translational control is more complex than originally described, underpinning its key role in diverse biological processes. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2025 Elektronická adresa https://www.sciencedirect.com/science/article/pii/S2211124724003048?via%3Dihub
Počet záznamů: 1